This invention relates to a method for the attachment of a biologically active material, e.g. ligands or immunoglobulins to the surface of flexible polymer substrate, and to a method for maintaining the biological activity of the attached biologically active materials by utilizing a water gloss overprint varnish matrix.
Although considerable effort and expense have been put forth in an effort to control food and/or airborne pathogenic microorganisms, there nevertheless exist significant safety problems in the supply of packaged food and in the certification of sterility for medically useful components, e.g. surgical tools, internal examination devices, e.g. endoscopes, and the like.
For example, numerous outbreaks of food poisoning brought about by foodstuffs contaminated with strains of the E-Coli, Campylobacter, Listeria, Cyclospora and Salmonella microorganisms have caused illness and even death, not to mention a tremendous loss of revenue for food producers. These and other microorganisms can inadvertently taint food, even when reasonably careful food handling procedures are followed. The possibility of accidental contamination, for example by temperature abuse, in and of itself, is enough to warrant incorporation of safe and effective biological material diagnosis and detection procedures. Further complicating the situation is the very real possibility that a terrorist organization might target either the food or water supply of a municipality or even a nation itself, by attempting to include a pathogenic microorganism or toxic contaminant capable of causing widespread illness or even death. If, by accident or design, the food supply of a particular population were to be contaminated, it is not only imperative that the population be alerted to the contamination, but it is further necessary that the particular contaminant be quickly and precisely pinpointed so that appropriate countermeasures may be taken.
With respect to medical or dental procedures, there exists a very real possibility for transmission of disease due to ineffective sterilization techniques or careless handling of medical implements, which can often lead to contamination of the sterile field. Although these devices are generally wrapped after sterilization, it is impossible to verify the efficacy of the sterilizing process or determine if subsequent contamination has occurred prior to use.
Thus, if it were possible to readily substitute standard packaging materials with a flexible material capable of
1) quickly and easily detecting the presence, and
2) indicating the particular identity of a variety of pathogenic biological materials, a long felt need would be satisfied.
U.S. Pat. No. 6,051,388 discloses bioassay materials which may take the form of packaging materials for food or other products and which are useful for detecting toxic substances The biological assay therein disclosed broadly encompasses a base layer which is a flexible polyolefin film having a surface which has undergone a treatment step effective to enhance the film""s ability to immobilize a ligand which has been applied thereto and a biologically active ligand which is immobilized to the film subsequent to which a protectant layer in the form of a gel coat or liquid film is applied. This patent requires separate deposition of the active ligand followed by application of the protectant layer.
U.S. Pat. No. 4,966,856 discloses an analytical element having a layer for antibody/antigen binding but fails to teach or suggest a flexible polyolefin matrix.
U.S. Pat. No. 4,870,005 teaches a multi-layer analysis element including a membrane filter to which an antigen or antibody is immobilized. The concept of forming a flexible analysis element having immobilized biological agents bound thereto is neither suggested nor disclosed.
U.S. Pat. No. 6,020,047 discloses a polymer film coated with a metal alloy and containing a self-assembling monolayer printed on the polymer film.
The prior art fails to teach a single step methodology wherein a composition functions as a carrier or vehicle for purposes of application of a biologically active ligand or the like to the surface of the flexible polymer while simultaneously acting as a viable matrix for maintaining the biological activity of said material.
The present invention relates to packaging materials for food, medical devices and the like products wherein the presence of pathogenic microorganisms is undesirable, along with methods for their manufacture and use. The presence of undesirable biological materials in the packaged material is readily ascertained by the consumer, merchant, regulator, etc. under ordinary conditions and without the use of special equipment. A multiplicity of biological materials threaten our food supply. The present invention provides a unique composite material capable of detecting and identifying multiple biological materials within a single package. The biological material identification system is designed for incorporation into existing types of flexible packaging material such as polyvinyl chloride and polyolefin films, and its introduction into the existing packaging infrastructure will require little or no change to present systems or procedures. Thus, the widespread inclusion of the biological material detecting system of the instant invention will be both efficient and economical.
In one embodiment of the invention the biological material detecting system prints a pattern containing several of the biologically active agents, e.g. antibodies or aptamers onto a flexible material which is usually a type of polymeric film, preferably a polyvinyl chloride or polyolefin film and most preferably a polyethylene film which has undergone a surface treatment, e.g. corona discharge to further enhance the film""s ability to immobilize the antibodies upon its surface.
Each biological agent, for example an antibody, can be tailored so as to be specific to a particular biological material and may be printed upon the flexible substrate in a distinctive icon shape. The detection system may contain any number of biological agents capable of detecting a variety of common toxic microbes; although any number of microbes may be identified via the inventive concept taught herein, for the purpose of this description, the microbes of interest will be limited to E. Coli, Salmonella, Listeria and Cyclospora.
The biological material detecting system will not merely detect the presence of biological materials, it will also identify the particular biological materials located in a packaged product. This unique feature allows for the immediate identification of each particular biological material present since the antibodies are specific to a detector having a definitive icon shape or other identifying characteristic. Although the end use consumer is primarily interested in whether a food product is, or is not, contaminated per se, the ability to detect and identify the particular biological material immediately is of immeasurable value to merchants, processors, regulators and health officials. The ability to immediately identify a toxic material will lead to greatly reduced response times to health threats that might be caused by the biological material and will also enhance the ability for authorities to locate the source of the problem. One means of providing enhanced sensitization is by including a scavenger antibody, which is a biologically active ligand characterized as having a higher affinity for the particular toxic substance than the capture antibody. The scavenger antibody is provide, e.g. by mixing said scavenger body with the combined capture antibody/water gloss overprint varnish, in a sufficient amount to bind with the particular toxic substance up to and including a specific threshold concentration. In this manner, the capture antibody will be prevented from binding with a detector antibody until the concentration of the. particular biological material surpasses the specific threshold concentration. In this manner, the biological material detecting system visually reports only those instances where concentration levels are deemed harmful by health regulatory bodies.
The biological material detecting system of the present invention exhibits an active shelf life in excess of 1 year under normal operating conditions. This enhances the use of a biological material detection system on products which are intended to be stored for long periods of time. If these products are stored so as to be ready for immediate use in some time of emergency, then it is extremely beneficial to definitely be able to determine the safety of the product at the time that it is to be used.
The method of production of the biological material detecting system is designed to be easily incorporated within the packaging infrastructure of existing systems without disruption of the systems or the procedures under which they are operating. The biological material detecting system can be incorporated onto packaging films which are produced by the packager, or those which are supplied by a film manufacturer. The apparatus necessary for applying the biological material detecting system may be easily located within any continuous process such as printing or laminating and will operate as an integral part of an existing system.
The biological material detecting system of the instant invention represents an entirely new packaging material which is designed to inform the consumer of the presence of certain biological materials or pathogens present in food stuffs or other materials packaged within the detecting system. The system is designed so that the presence of a biological material is presented to the consumer in a distinct, unmistakable manner which is easily visible to the naked eye.
An important feature of the biological material detection system is its all-encompassing presence around and upon the product being packaged. Since the biological material detecting system is designed as an integral part of 100% of the packaging material and covers all surfaces as utilized, there is no part of the packaged product which can be exposed to undetected microbes. In the past, the use of single location or in situ detectors have left a majority of the area around and upon the packaged product exposed to undetected microbes. This greatly increased the chance that a spoiled or tainted product might be inadvertently consumed before the toxic agent had spread to the location of the in situ detector. The biological material detection system of the present invention avoids this problem by providing a plurality of individual detectors per unit area which are effective to insure positive detection of any pathogenic microorganisms within the product being tested.
The present inventors have now discovered a method of printing which utilizes a type of Water Gloss FDA Overprint Varnish, e.g. (WVGOO 1006, available from Water Ink Technologies) as a matrix. These varnishes are commercially available and commonly used in the food industry. The product meets the requirements of Federal Register 21 CFR regarding polymeric coatings (Part 175.300) and components of paper and paperboard in contact with dry food (Parts 176.170 and 176.180).
It is an objective of the, present invention to provide a biological material detecting system for protecting the consumer by detecting and unmistakably presenting to the untrained eye visual icons on the packaging material which signify the presence of a number of pathogens in the food stuff or other materials which are at a level harmful to humans.
It is another objective of the instant invention to provide a bioassay material wherein an antigen detecting antibody system is immobilized within a biological activity maintaining varnish matrix upon the surface of a flexible polymer.
It is still another objective of the instant invention to provide a bioassay material wherein an antigen detecting antibody system is immobilized upon the surface of a flexible polymer film.
It is a further objective of the invention to provide a biological material detecting system which is so similar in appearance and utilization that its use, in lieu of packaging materials, is not apparent to the food processor or other packagers.
A still further objective of the present invention is to provide a biological material detecting system which is cost effective when compared to traditional packaging materials.